It is a deeply frustrating position to be in, wanting to work on these rare diseases and help this rarified patient population and not being able to, even though me and my colleagues are poised to do so. I often get maligned for being a scientist in pharma; laypeople often assert that I "don't want to treat cancer / rare genetic disease / etc; because then I'd be out of business." I can assure those reading that all of us DESPERATELY would like to work in these indications, and often times it's tragically finance that dictates whether we are able to or not. The system feels broken.

I understand that there are no easy choices here, and having to make a choice will always be heartbreaking.

May I suggest contacting MacKenzie Scott (Jeff Bezos' ex) who seems to be looking for worthwhile endeavors to finance.

(I have no connection to Ms Scott, I just read articles about her charitable activities in the newspaper.)

Both. We're not even close to our limits on research capacity.

If we actually were at the limits of research capacity, and we were actually forced to make decisions between livesaving treatments to research where we couldn't do both without sacrificing something else that saves lives, then yes, of course, choose the thing with the highest number of predicted lives saved. But we're not even close to needing to make such decisions yet.

We just don't have a good system for funding cures you can't sell to millions. That's not anywhere close to "heartbreaking decisions" territory; that's "societal coordination problem" territory.

(Full disclosure: close family member works at $bigPharma)

I don't think it's about finding treatments you can "sell to millions", it's that in pharma, like in pretty much every other business, it's about ROI.

You definitely don't need millions of patients, but you do need to cover the R&D costs _and_ have enough left over to keep the shareholders happy.

It may well be(!), so let's assume you're right, what better incentive structure should we put in place instead?

Increase general taxation and use that to fund more pharamaceutical R&D?

For many politicians that would be seen as a "courageous decision" (hat-tip: Sir Humphrey Appleby)

> and let them only be at-cost (!) manufacturers

Won't it be hard to find investors if you do that?

> move all R&D off to universities

I think the "D" in "R&D" might be the problem in this approach. Universities are great at many things, including research, but based on my experiences (science PhD two decades ago in a research group which worked on anti-infectives) the scientists there aren't necessarily very good - or even actually interested - in development as such. We partnered fairly closely with $bigPharma at the time, and they funded a fair chunk of our work.

Better that than paying negative interest for German 20 year bonds, if you ask me.

> Universities are great at many things, including research, but based on my experiences (science PhD two decades ago in a research group which worked on anti-infectives) the scientists there aren't necessarily very good - or even actually interested - in development as such. We partnered fairly closely with $bigPharma at the time, and they funded a fair chunk of our work.

Agreed, universities have historically not been involved into the development part. But that is not a given dogma that can't be changed - the government could fund the establishment of development departments.

Alternatively, international governments could establish cooperative efforts to develop pharmaceutical compounds. Rare diseases and the decline of available reserve antibiotics are a global problem affecting every country on Earth just the same.

Development = taking a lot of candidate compounds and evaluating them in the classic three-stage procedure - phase 1: determine how the compound is processed in actual human bodies to check if it is actually safe to ingest and what side effects can already be observed (n ~ 20-80), phase 2: determine effective dosage (n ~ 100-500), phase 3: check effectivity in a double-blind trial (n ~ 1k-10k), as well as the fourth phase (after-license monitoring) [1][2].

The more a compound progresses, the more expensive the trials get to conduct, not just because the participants usually get some compensation for their risk, but also because all the data has to be tracked and processed. And a lot of candidate compounds fail somewhere along the path (either because they are ineffective or because the side effects are too severe), which makes the money invested effectively wasted (from a capitalist point of view, not from a scientific!).

[1]: https://en.wikipedia.org/wiki/Clinical_trial

[2]: https://studienteilnehmergesucht.de/ratgeber/die-vier-phasen...

At least one $bigPharma defines "research" as being everything up to and including the first proof of concept in a human [Phase I] trial. After that would be "development".

My grandmother had rheumatoid arthritis, and it made her life utterly miserable for her last 10 years. Recently, Enbrel was developed by a biotech for profit company, it is the first effective treatment for rheumatoid arthritis.

No university or government came up with it. A for profit company did.

Take the US military budget and give it to life saving research instead of life taking.

Edit: Also implement a wealth tax instead of income tax. Discourage hoarding of wealth and concentration of power in the hands of top 1%.

Not in % of gdp. The only metric that matters. The US economy is massive in size so of course the budget is a big number.

> one of which is china manages to defend itself with a tenth of the budget.

Everything is cheaper in China. You can do a lot more with one million there than in the US.

edit: BTW, is there any actual proof that this whole military budget dissuades Russia and China in any way?

It has produced far, far better results than communist incentive structures.

Maybe not at your stage of research, but it's my understanding that further down the pipeline (eg clinical trials) you're mich closer to the limits, simply due to financial constraints: given that a trial for something you can sell to millions isn't that mich more expensive than one you can sell to dozens,and given that you need to get payed for your job, i don't see how it doesn't make sense to prioritize the lower hanging fruit. Am i missing something?

Maybe twenty years from now some people with a high degree of knowledge, skills, and some resources will be able to get around these hoops illegally (by the laws of certain jurisdictions) and fix these conditions (or kill themselves or somebody else trying, but so does god/nature and doctors, with different[citation needed] probability distributions).

Really? From the outside it seems to me like we are beyond our limits on research capacity.

The progress seems to be slowing down everywhere while the price per discovery of a new drug skyrockets with many having rather disappointing efficacy (high NNTs).

I think that more people studying rare diseases would result in a net gain of lives saved; I don't think it's as zero-sum as "either 1 person's life is saved or 10 are" in this instance.

Research also cross pollinates across disease areas. For example, understanding altered metabolism in cancer can yield insights for non-oncological metabolic disorders. Oftentimes, though, nobody's working on translating that work out of a cancer model, because the financial incentives are not there.

there are some examples, for instance enzastaurin being repurposed for vascular EDS, after washing out as an angiogenesis inhibitor for cancer. I don't know if it makes sense mechanistically, I sure hope it does.

The 1962 FDA effectiveness mandates have had the side effect of increasing drug development costs enormously, and that shuts down development of treatments for rare disorders.

The Kefauver Harris Amendment you refer to was immensely important towards the development of safe and efficacious drugs -- I do not see the connection between that act and rare disease therapeutic development. In fact, drugs that only offer marginal improvements in quality of life for rare genetic disease patients are often fast-tracked by the FDA. Requiring that a drug _works_ shouldn't inhibit drug development. Otherwise, we end up with tragedies like what happened with the use of thalidomide, which prompted this amendment in the first place.

Sure, competition also creates waste, which is your main point here, but don't discount the upsides.

Competition has proven itself in the real world. Having only one monolithic vaccine maker (whether for-profit, non-profit, or government) would be a very bad thing. What would happen if it falls to corrupt leadership, as one of many examples of how this could go wrong? There is no mechanism to escape badness here, because we only have 1 of them.

Large scale collaborative scientific endavours like CERN show us that it is possible to both publically share knowledge and still explore multiple avenues and competing designs. There's also no financial profit motive and while CERN receives a lot of public funding, it has to pump that funding back into the economies of the funding countries so it serves more like a high-tech industry stimulus and technological incubator.

I see no reason why a similar aproach for the development of (specific) therapeutics could not work.

Much larger cooperative structures are less proven to work and are more hypothetical, though, even if CERN is an example of such a structure working. The risk, mainly, is that there isn't a good corrective mechanism if the whole thing becomes corrupted or rotten from the top. The other risk is that the cooperation is actually detrimental to progress because it correlates outcomes via group think. Some decorrelation is nice. I am happy that Musk et al. weren't forced to become cogs at NASA, and could explore their own ideas, which was easier to achieve by then being explicitly separate entities (even if they were reliant on contracts).

the profit motive in a multinationally funded system is still there in the sense of 'we have a budget of X, what's the best way to spend it?'. And research avenues that fail to yield the expected results can be terminated. In my experience, disagreement between researchers or groups were also far from uncommon. But maybe that's just physicists being exceptionally knowitall^H^H^H hard to convince :)

It's not flawless, but I don't think it could be less efficient use of public money than the current system where we publically fund early research and the succesfull projects get snatched up by the industry, patented, and sold for large profits. Even if a lot of pharmaceutical research ends up going nowhere (or a competitor beats them to it), we still end up paying for it trough the profit margins of the parent companies.

Raising healthcare costs are a serious concern for many countries, and part pharmaceuticals are a non-trivial part of the cost. Researching and producing them locally might help reduce that cost and stimulate a broader healthcare industry.

I do fear that pharmaceutical research might be to politicized for a multinational approach(e.g. HIV, what disease to prioritize). And there's bound to be some backlash from certain groups over a large 'shadowy' multinational body doing human trials.

If we can use a software analogy, mess like Windows 95 wouldn't see the light of the day. But they were useful nonetheless.

The diseases like what OP is dealing with are the ones that are going to advance science for all of us. That’s where gene therapies are going to be applied first which will pave the path for more mass-market treatments.

I hope we can get in touch somehow. Thank you.

I'm familiar with the idea of re-purposing drugs for rare disease treatments (most of my adjacent work has been in very early-stage academic research), but I'm curious about the financials here. Could some of the financial risk here be minimized by aggregating multiple groups of patients, all suffering from different rare diseases? From what I know about the process, the answer is yes, but I'd be curious to hear from somebody closer to the process.

Personally, I'm a computational/mathematical biologist and I work on single cell data targeting multiple myeloma, I'd really like to see serious non-profit Pharma. Drug repurposing seems like the most feasible avenue. What I know of right now is open Pharma [2].

[1] https://dtp.cancer.gov/timeline/flash/milestones/M3_CCNSC.ht... [2] https://www.ospfound.org

[1] https://clue.io

Are there any possibilities that you see from your experience in using modeling or other in silico methods to reduce time in the lab, find new leads in drug development, or otherwise enhance research capabilities?

As far as in silico, I think absolutely there are probably opportunities here. Generative models might be useful for some type of counterfactual (automated) reasoning with respect to disease course/treatment. I think we're in the relatively early days of collecting high resolution cellular data, so I think in silico approaches like this will be more and more relevant.

Perhaps the interesting thing would be to ask what particular thing makes the US different to other western countries, rather than cherry picking one particular thing that happens to agree with whatever ideology is popular today.

Obviously this can't work in the current pharma industry configuration; what financial incentive is there for big pharma companies to publish their results for another company to beat them to a new drug? I don't have a solution to this problem, but I hope someday we as a society can find one. This would absolutely revolutionize biopharmaceutical science.

I've thought that a type of cryptographic data commons based on multi-party communication [1] could possibly be deployed with some effect. Basically you need algorithms that can compute on encrypted data, and a way to securely communicate encrypted data. There might not be huge incentive to use something like this, but maybe a version of this idea could work.

[1] https://en.wikipedia.org/wiki/Secure_multi-party_computation

I only have a rudimentary understanding of blockchain technologies, but a system where pieces of a research puzzle are stored on chain and each user can claim ownership of those findings, a resultant drug's profits could be proportionally split by every entity which contributed to the research.

Another idea would be to completely socialize all biopharmaceutical research, but that type of system would require an extremely radical societal shift.

> but a system where pieces of a research puzzle are stored on chain and each user can claim ownership of those findings, a resultant drug's profits could be proportionally split by every entity which contributed to the research.

I think ultimately this is how a research cooperative could work. If distributing and re-allocating fractional ownership is efficient enough, it seems like something like this might be feasible. The idea with multiparty communication (MPC) is that in this setup a research entity would contribute their data in an encrypted fashion, and any parties would be granted access to compute on it based on some set of rules/buy in etc.

This is a really difficult technical approach, as MPC is really only in it's infancy, made only to seem easy by the far more difficult and distant prospect of socializing medicine, which would seem to be of the greatest benefit.

When Martin Shkreli bought the rights to Daraprim, some of his rhetoric about pharmaceutical industry sounded fair. He said that he is willing to send the drug for free to anyone who wrote to the company and he was essentially making the insurance companies pay the absurd price of the drug. He claimed no patient would ever financially suffer for the drug. He said the needed the money to pay for new research and better drugs and it was one of of lesser of evil thing he can do to R&D.

Ignoring the trickle down effect, if the government and Insurance companies in most cases ultimately pay for the price of medication wouldn't it be valid motivator to research rare diseases?

Shkreli's ideology was when it comes to innovation in Pharma and America's patent driven capitalist nature towards it is the reason why America leads the way in innovation.

I guess for decisions about pharma research like this having an elected body or representation of an elected body is a good thing.

In the USA the best of the best are put in charge of tomorrows medicine, and that is why they succeed while the rest of the world is just pitiful in comparison.

Not sure if there's as viable for OP since only a few hundred people have been diagnosed.

I'm just extrapolating incentives. Is there any incentive to cure (invoice once), when they can treat (life long invoices)? Certainly scorn is irrelevant as OPs comment suggests they're unwilling to work on rare diseases. And these companies are public. They have shareholders that expect them to constantly grow.

I don't believe it's a stretch to say, at the very least, the incentive is there.

You know many people who would have died of smallpox,measles, polio, and the like 100 years ago, you just have no idea who those people are.

To be clear, I still think this conversation goes on in the background. Bill Gates famously convinced Oxford not to give the covid vaccine IP away thus preventing poorer countries from creating their own vaccines. The deaths from this act alone should be enough to convince you that money makes medicine murkier than you clearly want to believe.

Here’s a good post, he’s a prolific blogger: https://matt.might.net/articles/rare-disease-internet-matchm...

(Edit: this is a bigger picture post detailing the whole process: https://matt.might.net/articles/my-sons-killer/)

Depending on the kind of research you are looking to get funding for, you might also look into an NIH SBIR grant or something. https://rarediseases.info.nih.gov/tips/pages/124/

Also, I've put much of what I've learned online:

https://bertrand.might.net/articles/algorithm-for-precision-...

As you note with a patient pool of the order of hundreds, they are likely to be very scattered and so if you can get together a cohort for a medical trial, it makes it much easier for Pharmaceutical companies to test repurposed drugs against that cohort.

* I think it was linked to here on HN. Apologies for the shoddy search terms but the only things I can remember about their story was: the parents both dropped out of software jobs to get biochem (or biomed?) PhDs to research the disease (don't remember what) and the ease of cohort accessibility was their number one takeaway for their retrospective blog post(?). If you can find that blog post its well worth a read for all the non-technical (i.e. logistical/financial etc.) aspects of rare disease research.

A good friend of mine founded a startup to try and solve this and I was about to join her full time when the pandemic unfortunately crushed it, especially as they couldn't find a real business model.

It would be quite interesting as a non-profit entity though.

I feel your pain about wanting more R&D around treatments and potential cures but finding almost nothing because it wouldn't be commercially viable.

My main strategy was trying to contribute with what I know best: software development. The company I joined (lifebit.ai) is building tooling to reduce medical/pharma R&D costs, in an effort to make it economically viable to research diseases that weren't viable before. This is a mission I can get behind and that feels like the best use of my time.

I hope you get to find the best way to have the biggest impact. Good luck!

1. AllStripes (https://www.allstripes.com/) -> It might be worth reaching out to them to get put in contact with other foundations that might be working on the same thing.

2. Reaching out to RareBase (https://www.rarebase.org/) or Ethan Perlstein (https://mobile.twitter.com/eperlste) to talk about how they work with similar foundations.

3. There is a new company called (https://www.vibebio.com/) that are working on helping fundraise for patient communities using DAOs. I think Alok Tayi is one of the founders there.

4. I know there are some tech founders with family members of rare disease that have gone through similar experiences. For example, I think Rohan Seth at clubhouse has one (https://www.lydianaccelerator.org/). They might be good resources to reach out too.

our family experienced something similar when a loved one fell ill and therapeutic options were unavailable. feel free to ping me at atayi@vibebio.com - happy to connect and see how we can help.

our vision is to realize every cure for every community. rare diseases is where we are starting.

and thanks Sri for the shout-out!

However, for a player like me, it’s worth me operating in the 500k to 25mil range and buying businesses there because, first off I’m not a millionaire, and second, I can assemble a group of related small businesses which collectively would make 25 million which I can then sell to private equity for a larger multiple than I bought them for.

My point being, is there a way to create some kind of collective of rare disease causes and raise money as a group, collectively funding the labs and salaries of scientists to work on these diseases, ideally in an efficient way so that the work done on one disease can, at least partially, be effective for a number of the diseases in the group.

I don’t know the answer, I just wanted to offer an idea from my perspective.

So, a win-win emerges: PSP patients get well-funded clinical trials of therapies designed to address their affliction and the entire world gets improved understanding of therapies that target Alzheimers.

If there is something special about KS that allows it to be a diagnostic for therapies in adjoining disease with broader impact, then suddenly an avenue opens for intense investment in therapies for KS.

Universities have something called an indirect rate. This is basically how they pay for things that a private company would build into the overall cost of the project. Things like administrative folks, and lights, and heat, and IT support for the internet, etc., because "direct costs" are only what applies directly to your project.

These are often 50%+, and tend to come as a shock to people, even when the total cost is well less than private research firms.

The thing that doesn't get talked about as much is if you're a funder, if you have somewhere on your site, the funding announcement, etc. that you're capping indirects at say, 15%, that it's much easier for researchers to convince university administration to use that lower rate (in that if you don't have it, we're SOL).

So if you do ever manage to head that direction, please do make sure to include something like that.

I know people say "Autism can't be cured" etc. But having met other families in this process and visiting group homes and the potential for a life of happiness for kids like ours my hope grows bleak and I honestly catch myself crying when alone. Especially seeing neurotypical children playing or how other parents don't see the gift of a natural life their families have. I too turned to all sorts of exotic ideas of diets, behavioral therapies, vitamins and it was out of desperation. I put my daughter through a stem cell study at Duke that seemed promising but I then saw danger of losing potentially my daughter to experimentation. I was told by neurologist and psychiatrist that my daughter would never talk, never interact with the world. Today she's talking. I credit ABA, stem cell infusions, and a diet focused on fat consumption (basically keto) but in that same vein I've also learned to accept our fate.

Now I've cut way back and I just enjoy the gift of being with her. Her gains and triumphs whilst they pale in comparison to a neurotypical kid are harder but just as monumental. I know now the best thing parents or families in our position is to create a world that would accept our kids, take care of them, and create for them a place where individually they could have a fulfilling life. Yes a cure would be great but there are so many kids with different conditions, illnesses, accidents and circumstances that will have denied them a future. Modern day society doesn't adequately cover what children like ours will need when we are gone.

About twenty years later, he was grown up and was soon to have a family, when the son of a family friend was diagnosed in infancy with the same form of cancer - except it was even more rare. This strain is almost always manifested below the neck (like my uncle), but in this child, it was in his brain. It has been a battle, but the boy was able to fight through it several times. Multiple resurgences later, he is finally recovered: thanks to the research done on my uncle.

All that to say, research on rare diseases is extremely important and something I am very passionate about.

NIH provides funding and accelerator programs for medical startups. If you have the expertise, apply yourself, or find a grant writer to help you fill it out all out. The programs themselves are great and they provide a ton of support. Funding is in steps (e.g. step 1 - $200k, step 2 - $1mil).

I'd also recommend https://wefunder.com/ of who I know many of the folks running it and it is great, but the NIH route is more specific to your case.

There are tricks to this kind of stuff, and some people know the tricks. I guess the first step is knowing that it's a real skill, that people know how to do it well and you need to learn from them. I suspect they'd be willing to share them given the circumstances.

Now their existing donors may also be helpful, but you seem to be jumping a step.

I find it serendipitous that we just had a two hour call today discussing our desire to work on creating a treatment for one or more rare diseases.

The one area we lack expertise in is the regulatory and commercialization pipeline. If someone reads this and is interested in speaking with us about how we can work on this (or other) rare disease and could offer the mentorship we need to ensure our work can actually reach the hands that need it, please email me: josh@everymanbio.com

We'd consider a non-profit model if it makes sense.

Even if pharmaceutical company profit weren't an issue, limited resources still would be a problem, so very rare diseases would still suffer from lack of attention, I'm afraid, because if we replaced "what research produces the most profit" with "what research benefits the most people", that still wouldn't help KS sufferers much. Perhaps the kind of fundraising you are doing is the best that can be done. Or maybe some line of research that can benefit sufferers from multiple diseases (say, anything that results in a missing protein) could help a larger number and obtain government funding.

Your ideas all sound fantastic, and definitely on the right path, maybe reaching out to foundations of other rare syndromes may offer some help, likewise with Facebook groups, and the like. I run my own non-profit https://sterlingstrong.foundation to bring awareness to KS, CHD, isomerism, etc, and to help families during long ICU stays, and further research by donating to other research centers such as https://www.kennedykrieger.org, maybe they, or orgs like Center for Rare and Neglected Diseases https://crnd.nd.edu/directors-page may help? I wish you and your family all the best!

Community building will be an important part of your foundation and parents. In our case, we joined the SETBP1 support group on Facebook. It is always heartwarming and comforting to read other peoples and to know that you are not the only one that is in a similar situation. The Facebook group keeps us also updated on recent scientific progress and we were able to join a research study on SETBP1.

I know that having a kid that is unable to communicate is hard. Very hard. When our son was younger he was sometimes very frustated because he could not express himself. But communication is more than speech. Our son is now mainly expressing himself with key word signing (in our case the Dutch variant SMOG) and his speech is gradually improving (at a very slow pace). I hope your daughter will also find a way to properly express herself.

[1] https://rarediseases.info.nih.gov/diseases/13379/setbp1-diso...

[2] Morgan A, Braden R, Wong MMK, Colin E, Amor D, Liégeois F, Srivastava S, Vogel A, Bizaoui V, Ranguin K, Fisher SE, van Bon BW. Speech and language deficits are central to SETBP1 haploinsufficiency disorder. Eur J Hum Genet. 2021 Aug;29(8):1216-1225.

[3] https://www.setbp1.org/

Just chiming in as my son too has an 18q deletion, albeit further towards the distal arm. Just to bring to your attention, if you were not already aware, of https://www.chromosome18eur.org and its parent organisation https://www.chromosome18.org.

Some great resources and there'll be folks who have experienced similar issues to you and yours.

> How to raise funds for rare disease research?

I'm not a marketing expert (though I do work with rare diseases). But a good starting point might be to checkout https://www.rarebeacon.org/ There certainly is help and there are options, but as you understand finding and accessing them isn't always easy. Good luck on your journey

I'd start with a simple campaign page with your mission, your goals, some cute pics and some way to collect donations and capture emails. There's loads of fundraising CRMs out there. Givelively is a decent one and costs nothing but there's plenty of options. Even just a Facebook page could work.

As for how to acquire leads from scratch that's a tough one. Ads can work, you can also try reaching out to media orgs to try to get some airtime to talk about your campaign.

https://chanzuckerberg.com/science/programs-resources/rare-a...

Meta aimed to build a knowledge graph of published research papers.

Patient driven research/rare is one is a separate program focused on supporting patients with rare diseases connect with and support scientists studying those diseases and the larger rare diseases network.

This is what they specialize in. Feel free to e-mail me if you need help getting the conversation started there, I know a few of their MDs and researchers.

EDIT: Apologies, I see this has already been recommended and Matt has himself replied. Best of luck!

The best I can see is to invest very heavily in the common methods underlying how the therapies get created - gene editing, knockout / interference etc. The better these work, the less risk there is that a drug is going to fail at clinical trials. It means, a lot more basic research as well as applied research to translate the findings.

Then we need to work on smoothing the clinical trials pathway as much as possible so that if a method is operating from proven principles it doesn't have to jump every single hurdle as if it is completely novel. Obviously, there are huge risks here if it goes wrong. But on the other hand, we can look at the cancer space and see that patients get very ready access to experimental drugs there, and overall it is enormously beneficial to overall progress. Rare disease sits somewhere in the middle - people are not (usually) dying but their life quality is so heavily compromised that there ought to be some allowance for a more accelerated access to trial drugs than if we are talking about routine medical use.

Next, we have to understand that there are serious ethical considerations on treatments that target embryos. Biology is still very much a black box field. It is near impossible trying to factor in all the parameters in this problem space, especially when you are altering genes at a highly regulated stage of human development. Millions of model organisms like mice and non human primates are used to test therapies, but would we be willing to do the same to human embryos at such a large scale? I would hardly imagine an IRB approving research like this in my lifetime in the U.S.

The other kind is about drugs that are out of patent, like Ketamine, which very likely can cure important diseases, but since no one stands to make back the money it costs to get them approved, they remain illegal.

Of course, I'm not at all a billionaire, but some of them read HN.

Please do try and make contact with Dr. Jannine Cody[1] who when faced with a not too dissimilar position to yours pretty much single handedly set about doing what she had to in order to understand and improve her daughters condition and in the process has created a worldwide network of families that meet at conferences and fund research.

Good luck, know that you do not stand alone. It might seem like you do, but you'll be surprised.

[1]: https://www.chromosome18.org/chromosome18-team/jannine-cody/

The story of how CF treatments developed (Trikafta) is remarkable. KS seems much rarer than CF, but I recommend studying how the CF Foundation evolved. https://www.cff.org/about-us/our-history

There are lots of good suggestions in the thread. It seems you're already doing this, but I recommend connecting with people (e.g. families of those with KS, medical professionals with an interest, marketing volunteers, ...) and keeping in touch. This can help create momentum behind a movement, leverage networks, and mutual support/encouragement. We also very much appreciated connecting with others affected by CF during that time.

https://news.ycombinator.com/item?id=29287200

It also includes a link to this:

https://www.resetera.com/threads/guy-cures-himself-of-lactos...

The US government, since 1983, provides grants and streamlines drug development processes for development of drugs for rare diseases. The government calls them “Orphan Drugs” and defines them as drugs that treat diseases that affect less thank 200k people annually, and are not expected to be profitable within 7 years.

I believe that my friend said that pharmaceutical companies are actually required or strongly incentivized to research some number per year but I can’t find a reference right now.

https://rarediseases.info.nih.gov/files/fda%20orphan%20drugs...

PS: I'm actually going to try apply to work for AllStripes soon.. Wish me luck!

Though if you are trying to get clinical trials you may need more money, but just the act of having a lot of small donations can work wonders.

Of course some here will donate to your charity, and all money is useful, but consistant money is something you can budget around.

I am the founder of kernls.com, a giving-platform that connects motivated donors and medical researchers looking for funding. We work with some of the top medical research institutes in the world, and connect people like yourselves directly with researchers to support awareness and fundraising.

Check out the site, and if interested I would be really happy to chat, shoot me an email at mike@kernls.com.

What is the likelihood of research finding treatments that will reduce that cost, and by how much?

I wonder if a financial instrument could be crafted that captures a potion of future insurance company savings in return for funding research now.

Probably would require some concessional, first loss funding, or perhaps a philanthropic evergreen fund.

A therapy would reduce cost per patient by $x/year. Potential payment to investors in therapy could be 0.5x/year. Someone might be willing to buy that future cash flow now.

Hard to pull off: gotta build a consortium of all insurance companies in US, possibly national health systems in the world, get them all to agree on a current cost and value of a cost reduction.

Then have to have a reasonable degree of certainty in the cost to produce a novel therapy, and potential value of said therapy.

However, once you create the process for the first of these financial instruments, subsequent instruments should be much easier.

If there are many such groups of people with rare diseases, banding together to create the process could be a thing.

I imagine if you reach out and want to find ways to help / volunteer they would be excited to hear from you and to find a way to work together (most non-profits like this are...)

I'd even reach out to David and talk to him about it. His daughter was diagnosed with GM1. He used his media skills to tell her story, worked with the leading nonprofit in the space, reached out to bio-engineering companies to try to get his daughter into a trial...and they just had a fundraiser in LA.

Good luck!

https://rarevoices.org.au/

https://www.lydianaccelerator.org/

It is the project of a former colleague; I don’t know the latest status of their efforts

Did you talk with universities/academia? They have laboratories and students who may be will be glad to help.

They are a biotech hedge fund that has a non-profit team funding rare disease work. There should be a form on their website

They've not received much attention, nor do Western doctors/researchers have much to any knowledge at all in regards to what they're doing - because for the last 30 years they've been using fetal stem cells to successfully treat a variety of conditions; and last 25+ years offering treatment clinically.

Conditions like Multiple Sclerosis, which have "no cure" in the Western world, EmCell states and their experience is (which the documentary done by independent film maker follows at least one person treated for beginning MS symptoms) that if you treat MS earlier enough, before there's too much disease progression destroying the body's healing abilities, that the fetal stem cells will cause the dis-ease to stop progressive and even to regress (to heal) potentially fully (to be cured); multiple dystrophy, ALS, etc. are other "uncurable" treatments they offer treatment for.

As in the documentary it will be explained, they used fetal tissue that is 7-12 weeks of age, which is before the tissue begins to differentiate into that specific human tissue - before the immune system starts to develop, and so they argue it's safe to inject in anyone - as we all started from those base tissues.

I'd suggest looking at their website (which they updated recently so it's not as easy to navigate IMHO) but then also to email them to ask them specific about your daughter's issue. My guess is they at minimum would state that you could try to see if it helps - but maybe ask if they have treated other rare genetic disorders with any improvement seen.

Lately they've been diving into more specific research, like trying to improve fertility - injecting the testicles - which initial research showed a 30% increase in motility/health in sperm, etc.

They list a lot of success stories - https://emcell.com/success-stories/ - where they include (at least in their previous website they did) long-form video testimonials following them.

They also inject placental tissue into a patient's body, as placental tissue apparently has powerful anti-inflammatory and immune regulation mechanisms - so it's possible that a large amount of benefit may come from re-balancing/re-regulating the immune system however the placental tissue works to do so.

https://twitter.com/eperlste?lang=en

As for how to find/approach such companies, that's a tougher question. It's a great boon for a company to be able to get Orphan Drug designation[3][4], for which KS may qualify. Hurdles are lower and it can help them bring that treatment to approval.

One thought would be to examine company pipelines for drugs targeting this gene/pathway, even if it's for a different condition. For example, here's a press release[5] on a company with preclinical results for Sickle Cell Disease on a EHMT1 inhibitor (probably not what you need but at least related) and here's another[6] on a CDMO contracting to produce GLP protein for a client (it doesn't say who but at least indicates interest).

Another thought would be to look for companies targeting related conditions because at least they have the expertise and may even have a candidate (failed or active!) that could provide some benefit. The idea of a repurposed drug search is a good one if you can find something still under patent since you'll need someone with deep pockets to reach approval.

Note that these might not be pharmaceutical companies but biotechs instead, the distinction being small-molecule (chemical) vs. large-molecule (biologic), respectively, as it's much more difficult for others to make a generic copy of the latter. To that end, you might add monoclonal antibodies to your list of potential modalities.

Sorry, I have no clue on the funding question. You mentioned several other foundations that had success; I'd suggest reaching out to them for ideas and strategy if you haven't already. I do know that some states have Life Science initiatives of various kinds which might offer grants/funding and may have associated incubators and whatnot where smaller players can "band together" to get shared access to equipment, lab space, expertise, etc. Unfortunately I don't have a link for that at hand but can try to dig up something if it's useful.

[1] https://www.forbes.com/2010/02/19/expensive-drugs-cost-busin... [2] https://healthcareglobal.com/top10/top-10-most-expensive-dru... [3] https://en.wikipedia.org/wiki/Orphan_Drug_Act_of_1983 [4] https://www.npr.org/sections/health-shots/2017/01/17/5095068... [5] https://www.globenewswire.com/news-release/2017/12/11/125070... [6] https://www.contractpharma.com/contents/view_breaking-news/2...