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Molecular Analysis Plays Important Role in Orphan Diseases

Jun 4 2019

Posted In:

20/20 Blog

Palo Alto, CA – Calling a disease orphan, or rare, can be misleading considering millions of Americans suffer from thousands of orphan diseases that are often serious or life threatening. Together these diseases constitute a serious public health concern, but they often receive limited pharmaceutical and clinical trial attention. Stanford retina surgeon, Vinit Mahajan M.D., Ph.D., Vice Chair for Research in Ophthalmology, believes that cutting edge molecular analysis tools will open up clinical trials and pharmaceutical opportunities and allow researchers to find therapies for rare conditions.

Compared to common diseases, there are fewer patients to study in orphan disease clinical trials. Diagnosis is often difficult, and there are a limited number of treatment centers with a few expert physicians. The long-time commitment and billions of dollars involved prevent drug companies from developing new therapeutics. However, an already approved drug may be the best way to treat an orphan disease if it shares similar molecular features with a common disease.

Molecular surgery approaches can shrink the pool of necessary volunteers for a clinical trial by identifying patients specifically based on whether or not they have the molecules that are being targeted by either existing or experimental drugs.Drug repositioning, which applies approved drugs and compounds towards new indications, is one of the most important outcomes of molecular analysis of eye tissues. Needing fewer volunteers and drug repositioning can lower the cost of clinical trials, making them more attractive and easier to fund.

Mahajan said, “Examination of liquid biopsies from the eye can identify molecules that can be targeted by available drugs.”

Dr. Mahajan and his team have had success in the laboratory using molecular analysis tools like proteomics, the large-scale study of proteins. They found disease molecules that could be targeted with existing antibody drugs and anti-inflammatory small-molecules.

Because eye surgeons know how to insert a microscopic needle into the eye, safely and precisely, without causing new bleeds, infections, or retinal detachment, drug delivery is direct and highly potent.

“Since we inject a drug directly into the eye, it does not get processed in the gut, liver, kidney, or blood. The drug goes straight to the diseased cells,” Mahajan said.

In the past, surgeons created the smallest, sharpest surgical blades to manipulate tissues, but now they can use enzymes to operate on molecules. The light microscope was the limit for finding surgical planes in tissue, but now cellular imaging and chemical labeling reveal molecules that define surgical planes. All of these advancements still depend on the exquisite surgical skill of an eye surgeon to safely and precisely deliver any molecule, to any cell, anywhere in the eye.

Translational research like Dr. Mahajan’s that bridges the gap between the laboratory and the clinic is bringing a new focus to orphan eye diseases, which could lead to a greater number of orphan disease clinical trials. As researchers gain a deeper understanding of the molecular mechanisms of these rare diseases, Mahajan expects it will shed more light on understanding more common diseases. 

“While most of the focus has been on vitreoretinal disease,” Mahajan added, “surgeons throughout the Byers Eye Institute are actively banking and analyzing surgical specimens from oculoplastic, corneal, and ocular oncologic disease. Soon we will gain a full spectrum view of the molecules we must target for common and rare eye disease.”