In order to find a targeted treatment for the >7000 rare genetic disorders, we first need to find the gene underlying each of them! There are two ways people can contribute to this goal: 1) Researchers and clinicians who work with families who have undiagnosed genetic disorders can apply for free exome/genome sequencing and analysis through our group and others (University of Washington Center for Mendelian Genomics http://uwcmg.org) 2) Families with undiagnosed disorders that are suspected to be genetic can share their symptoms and genetic information through an open access site like MyGene2 (http://www.mygene2.org). They can even apply for sequencing through the affiliated research study.
It is critical that everyone share data about rare genetic diseases openly because there are so many disorders and so few $$ available to spend on research. Everyone needs to work together!
9
Our evolving biotechnologies have enabled us to look beyond the “magic bullets” to a variety of “system biology” therapeutic approaches. The magic bullets while appropriate for such purely extrinsic diseases as infections, are less effective and often have significant toxicity for diseases with an intrinsic component.
System biology therapies are needed in disorders of our “maintenance apparatus” (whose components and operation, we are only recently focusing upon as an aspect of organismic biology). They would operate by normalizing the apparatus itself, rather than attempting to block or stimulate a particular target for a magic bullet.
Many common chronic diseases are candidates for such therapies. One theme for many conditions is inadequate removal and replacement of damaged cells or abnormal molecules (aka “garbage”), a fundamental responsibility of the maintenance apparatus.
Several special areas such as synthetic biology and tissue engineering are in active development.
As our understanding of the basic biology advances, we will be more and more able to rapidly develop personalized therapies using the patient’s own cells to enable them to return to “working” condition.
Steve Rinsler, MD
3
As an individual with an extremely rare, potentially life threatening, autoimmune disease that’s finally (finally!) managed by the brilliance of my doctor and the off label use of a long existing therapeutic, all I can say is: Doctor, I appreciate your focus and am truly grateful.
18
Both rare and many chronic disorders represent dysfunction of organisms’ maintenance apparatus, which is a component of each tissue and organ.
The current dominant approach to therapy - the magic bullet - is useful for infections and other extrinsic diseases, but is liable to limited effectiveness and significant adverse events for most diseases which have an intrinsic component.
For these, a systems biology based approach (so-called regenerative medicine is one) might provide better response without significant side effects, by working with/upon the organism’s maintenance apparatus.
The development of biotechnology in recent decades has spawned a number of disciplines (computational biology, synthetic biology, tissue engineering, etc) that offer the hope for such new system biology compatible treatments, in the relatively near future.
Stephen Rinsler, MD
4
@Stephen Rinsler--What about something like my daugher's disorder, a neurological condition that manifests itself in week 3-5 after conception. Fortunately she has a very unusually mild form, but it still impacts her daily life. And the NIH could find no genetic cause (even though it's sometimes found to be caused by SHH. ZIC2, SIX3, and TGIF1) so it must have happened due to some environmental condition, but the only one proven to be related is maternal diabetes, which I did not have.
2
@Susan With better surveillance now, we might understand some things better. And we can rapidly test for something that might be going around. I mean--look at Zika. That probaby did affect pregnancies for decades, but finally we found out about the impact just lately with rapid tracking and sequencing.
Fascinating. The Allen Institute in Seattle has a publicly available cell model that supposedly catalogues all known cellular proteins & interactions. Wonder if it would have recognized the otc solution (was it pylorsec? Can't get back to the article now)
1
Webeconcerned because this statement smacks of the topic of the 1997 movie 'Gattaca': "A pharmacogenetic panel that will tell you your response essentially to every drug on the market costs on the order of $300. And you’ll have that data for the lifetime of the patient. We’ll sequence everybody at birth at some point."
That last sentence is disturbing to us ... and maybe to you. It should be.
2
Fantastic stuff. I salute Matthew Might.
3
The genetic mutations that cause so many diseases cannot all be 'fixed' by known drugs. How can a young person suffering from Von Hippel Lindau (VHL) be 'cured' when the mutation causes their body to fail to produce the protein needed to inhibit the growth of hemangioblastomas in their brains and eyes and central nervous system and growths in the pancreas and clear cell carcinomas in their kidneys?
The compassionate doctor and his wonderful family are at least striving to find cures, but we need striving on many fronts. I am the mother of a child with VHL, a very rare disease that is inheritable but which she is the first in the family to suffer the consequences of.
Genetic mutations form a burgeoning area of scientific investigation and we need all the help we can get. Understanding VHL holds promise for understanding how tumors grow...who knew our bodies produce proteins to inhibit tumor growth? Here's to all the scientific inquiry aiming to reduce suffering. Please keep funding NIH.
7
DDC Clinic in Middlefield, Ohio, in the midst of an Old Order Amish community, has been doing this kind of research for a decade or more. They collaborate with The Cleveland Clinic. I hope Dr. Might will communicate with them.
1
There is now an NIH-driven a consortium of clinicians, clinical centers, and advocacy organizations to better study, understand and treat rare diseases, the Rare Diseases Clinical Research Network. About 200 rare diseases and 45,000 participants are already so engaged. This is an exciting development in this era where we can now connect to one another virtually and in person. Please see https://www.rarediseasesnetwork.org/ for details.
5
I know everyone was promised that the Human Genome Project was done and everything would be sorted shortly. But this stuff takes time.
What we have now, though, are much better maps and mining tools and targets. I was just noticing that TV ads now contain gene names (ALK and EFGR on the one I just spotted the other day). I know of people undergoing astonishing treatments that weren't available before.
It's coming. I hope that we can support the important research and let the solutions bubble up--on health, agriculture, conservation, and so much more.
1
Thank you for sharing the story of Dr. Might. It is inspiring on so many levels. He has used his own challenges to help so many others. He is a gift to not only Bertrand, but to our society. Bravo.
4
Though "A pharmacogenetic panel that will tell you your response essentially to every drug on the market" is an enticing goal, it is certainly not a current reality. This statement requires more investigation and push back from the interviewer. Firstly we frequently don't know all the gene sequences involved in the primary or desired action of a drug molecule, much less the secondary and tertiary which can be related to significant side-effects. In addition, genes are not the only determinant - age and physical condition will also have a significant impact. The statement is simplistic and requires further exposition.
9
Re-purposing existing drugs could be the most promising route to follow BUT still requires considerable investment of research $ and physician time. Not very likely with bottom line health care systems.
7
Inspiring! Dr. Matthew Might is doing outstanding work!
7