The Finding a Drug Discovery Partner (First) Edition of the Newsletter (10/17/21)

Hello CURE MED13L Community!

I’m Nick Seaver and this is the inaugural edition of the CURE MED13L newsletter.  I can’t tell you how thrilled I am to be kicking this off.

Since the MED13L Family and Research Virtual Meeting in August, we have made tremendous strides pushing forward the CURE MED13L Initiative.  Let me begin with two particularly exciting updates.

1. Drug Development: we are in discussions with multiple drug development partners and are close to selecting one to test thousands of already-approved drugs that may have a positive impact on MED13L.   We have been interviewing these partners, reviewing agreements and doing due diligence through other family foundations to select the best initial partner for CURE MED13L.
2. Funding: we already have funding to kick off this drug development!  We estimate that the first stage of this drug development will cost approximately $60,000. We are about to kick off a $1 million fundraising effort.  Thanks to a few generous and passionate MED13L families, we already have commitments for over $125,000 – enough to initiate this first stage of the drug repurposing effort!

I should also mention that another MED13L family has joined the leadership team of CURE MED13L.  They would prefer to remain anonymous but I would be remiss if I didn’t share that they have brought tremendous energy and thoughtfulness to the effort and it has been fantastic working with them. Together, we have been spending a lot of time speaking with potential vendors (drug development; mouse model; etc.) and partners (non-profits that support rare disease program development) and have been building relationships with a handful of amazing rare disease foundation leaders who are a bit farther down the road than CURE MED13L and have shared with us their hard-fought learnings. We have been assessing costs and benefits of various activities, in order to prioritize. We are working closely with Kelly Sexton (MED13L Foundation’s founder) on all of this.

Farther below, I list our highest priorities.  But first, let me address a question related to today’s main topic:

What exactly is a “drug development partner” and how can one help us?  A drug development partner is an organization with the skills and technology to conduct studies to find therapeutics for MED13L, including the repurposing of existing drugs and the identification of new drugs and ‘advanced therapies’ (like gene-related therapies, for example that promise to address MED13L at its root cause – the dysfunctional gene).  If you’d like to learn more, I would point you to the website for Rarebase, a candidate partner for MED13L.  They describe what they do at a high level on their homepage.  They have just announced their launch with 15 rare disease foundations already on their platform.  A drug development partner like Rarebase focuses on small-molecule therapies and can deliver an analysis of thousands of drugs to see if any upregulate the MED13L gene.  As many of you know, one piece of good news for us is that MED13L is a haplo-insufficiency disorder.  This means that patients have one healthy copy of the gene, so they are at least producing some amount of the healthy MED13L protein already.  If we can find a small molecule that upregulates the existing healthy copy of the gene to express more protein, then we may be able to improve MED13L in a relatively short period of time.  There are incredible recent examples of other foundations that have taken this approach and have been able to find already-approved drugs that can be repurposed for their disease – and they did so very quickly!  One foundation we spoke with recently found a repurposed drug this way in a few months, and a few months after that were able to initiate a clinical trial.  May we be so lucky.  More to come on these examples from other foundations in other newsletters.  Our hope is to have the good fortune of getting a “hit” with these initial assays and to be able to move forward with a repurposed drug relatively quickly.

In addition to selecting a drug development partner, we are also pursuing a large number of other initiatives, including (but not limited to!) the following:

• Finding clinicians (and their teams) to help drive forward CURE MED13L.  It is important to find physician-researchers who, with their teams, can lead clinical trials, help drive forward important research, meet with our patients and get to know MED13L, and perhaps even prescribe a repurposed drug “off label” if we are fortunate enough to find one that is safe and accessible.  As part of this, we are trying to enlist a post-doctoral candidate, ideally one who works with one of our MED13L Physicians.  This “post-doc” will work with us on a day-to-day basis to move forward CURE MED13L.
• Mouse models: critical tool for researchers as they work towards an “IND” package to start a clinical trial.
• IPSC’s: cell-lines from patients that can be used for research – also very important for researchers working toward a clinical trial.
• Obtain Insurance Recognition: This starts with getting what is called an ICD-10 code.  By working with the right clinicians and experts, we are going to lobby the CDC and the WHO to get a diagnosis code specifically for MED13L, which will help  us understand how many patients there are in the world; help doctors provide care; obtain insurance; and more.  See this Atlantic article on why ICD-10 Codes are so important.
• Natural History Database: also a critical tool for our community and for biopharma companies and hospitals that may carry forward a clinical trial. Natural history studies can be used to support the development of safe and effective drugs and biological products for rare diseases. A natural history study collects information about the natural history of a disease in the absence of an intervention. Although knowledge of a disease’s natural history can benefit drug development for many disorders and conditions, natural history information is usually not available or is incomplete for most rare diseases; therefore, natural history information is particularly needed for these diseases.  A good article on why, here.
• Gene-related therapies (the longer game): incredible new gene therapy technologies are coming up, including anti-sense oligonucleotides (ASO’s), gene therapies, and gene-editing (e.g. CRISPR).  A gene-based therapy holds the promise truly to cure MED13L at the level of its root cause, the MED13L gene.  There are important technical hurdles to get over still and this will likely take many years.  We will not stop until we achieve this ultimate goal.

There are so many promising things going on with CURE MED13L and so much more to discuss.  I’ll hit pause here.  Please feel free to share this note with anyone who may have an interest: researchers, doctors, donors, other rare disease crusaders – and of course other MED13L families.  Or share on social media (you can click three buttons in upper right)!

Gratitude is a gift that can help any of us stay buoyant on this long and sometimes difficult road.  Let me take a few moment of gratitude.  First: for the families that are helping out with CURE MED13L.  We couldn’t do this without you.  Then: a special moment of gratitude to Kelly Sexton, who got the ball rolling for all of us with the MED13L Foundation and who has supported so many.  And most of all, a moment of gratitude to her two beautiful boys Dylan and Logan, who are an inspiration to us all — and who inspired Kelly in the first place.