100 Years of Progress

In order to fix something, you have to know how it works. Now is the time to take the next big step toward medical treatments for VHL ... and it only took us 100 years to get here.

In 1904 a German ophthalmologist, Dr. Eugen von Hippel, wrote a case study of one of his patients with “a very rare disease of the retina.” It intrigued him. He carefully described what he saw, and learned through his experiences with that patient and his extended family. He continued to study and analyze “the anatomical basis” of the disease, which he named angiomatosis retinae, and the numerous lesions he found in several generations of that family.

Patience, precision, trial, and error

In science, solutions do not always come easily. Thomas Edison often talked about the number of tries -- and failures -- it took to invent the lightbulb. Edison was quoted as saying, “Genius is one percent inspiration and 99 percent perspiration.” It is that scientific curiosity, persistence, and ingenuity that we are applying today in the new science of genetic medicine. To truly “cure” VHL we would have to change the genetic code in every cell of the body. That is not an easy undertaking.

Description, Treatment, Diagnostics

Dr. James M. Lamiell described three epochs in living with VHL. From 1879 when the condition was first noted to 1929 when Lindau published his paper linking von Hippel’s angiomatosis to lesions of the central nervous system, we did not have a complete description of the disease. Diagnosis was most often made during an autopsy, too late to be of help. From 1929 to 1979 we saw progress in treatment, as surgical techniques improved, but it was still extremely difficult to make a diagnosis before symptoms demanded action. Beginning with the introduction of diagnostic imaging (CT, ultrasound, and MRI) we now have ways to see tumors growing before they become symptomatic, and plan better treatment before symptoms became critical.

Proteomics

We identified the VHL gene in 1993. It’s all well and good to say that you have the code in your hands, but can you read it? Not just the letters, but the words and the meaning of the sentences? Little by little scientists are unraveling the function of the VHL protein in the cell -- what it does, and what goes wrong when it’s not there. It has taken the same patience, persistence, trial and error that all great scientific discovery takes, and the VHL Family Alliance has helped to encourage a number of fine young scholars to focus on the VHL protein.

Now it is time to take the next big step -- taking that basic understanding of what’s happening in the cell and translating it into real therapies. Can we design a drug to intervene in the chain of events going on in the cell, correct the problem created by the absence of the VHL protein, and fix the outcome?

New Drugs and Clinical Trials

Fortunately for us, the VHL protein plays a key role in cell function and interacts with at least 20 other proteins, making it essential to good outcomes in many conditions, not just VHL disease. This means that the pharmaceutical companies are working on a number of drugs that are potentially beneficial with VHL. Three key pathways we know of at this time are VEGF, PDGF, and HIF.1 If there is too little VHL, these proteins are over-produced. There are drugs to block VEGF production, or to block the receptors that would normally respond to signals from VEGF, making the cell behave as if its VHL and VEGF function were normal. Some of these drugs have been well tested with other conditions and may be approved and on the market as early as 2004-05.

This means that we know a good bit about the safety and side-effects of these drugs, and that they work with colorectal or prostate or kidney cancer. What we don’t yet know is whether they are really effective with VHL tumors. And the only way we can find that out is to try them in a systematic way with at least 50 people with VHL.

If these drugs are going to be approved anyway, why do we need to do clinical trials with VHL? Once a drug is on the market at all, a doctor can always prescribe it for some other condition -- what is called “off-label use.” But if the drug has not been approved “for VHL,” your health insurance might decline to pay for it, because the drug is considered “experimental for VHL”. We might find ourselves in the unwelcome position that a drug is available, but not accessible -- out of reach economically.

We Need You

This new generation of drugs is not “chemotherapy” in the classic sense. Your hair does not fall out, the side effects are minimal, you can carry on a normal life while taking the drug. You don’t have to be in a desperate situation to want to participate in these trials, in fact it’s better if you’re not. If you are seeing a tumor developing in a position where surgery could cause a deficit, then you might want to discuss trying drug therapy to halt or shrink the tumor. It does take a commitment of time to assist the researchers in gathering the information we need to verify the effectiveness of the drug with VHL. It’s your personal investment in a better future.

These early drugs are only the beginning. If it was an allergy medication, would you pass up taking it waiting for a better drug to be developed? Or would you try this one and see what relief it might give you? When another better drug comes along in the future, you can always switch. Read all the fine print, ask every question you can think of, but please begin to consider: if you could halt or shrink that tumor without surgery, and if you have time to try a therapy that might take 6 months or a year to do it, would you like to try?

We want to take this opportunity to honor Dr. von Hippel for his critical contribution toward curing this disease -- giving us that first description, upon which has been built 100 years of progress. Now it’s up to us. We need your help! Thank you!