GDNF discovered

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Leu-Fen H. Lin, Douglas H. Doherty, Jack D. Lile, Susan Bektesh and Frank Collins, Synergen, Inc. (Boulder, Colorado), a biotechnology company. Science 260:1130–1132, 1993. Funding beyond the company is not stated in the abstract.

What happened

Since dopamine loss is the core of the disease (landmark 1), a protein that protects those cells was an obvious search target. The team purified a protein from a glial cell line and cloned it. GDNF is a "disulfide-bonded homodimer" (two linked identical chains) distantly related to the TGF-β family.

• In cultures of embryonic midbrain, recombinant human GDNF increased survival of dopamine neurons, helped them grow, and raised their dopamine uptake.
• The effect was fairly specific: it did not raise total neuron or astrocyte numbers, nor uptake by GABA or serotonin neurons.
• The authors suggested it could be useful in Parkinson's disease.

Why it moved us toward a cure

It started the growth-factor idea: feed or protect the neurons instead of replacing them. It led to infusion trials and then gene therapy (landmark 39).

Outcome

Advanced. The molecule worked as hoped in cultures. Clinical results are mixed: infusions improved scans but not patients, and the gene therapy AB-1005 is in a sham-controlled Phase 2 (landmark 160; history in landmark 39).

Sources

• Lin et al., Science 1993;260:1130–1132, DOI 10.1126/science.8493557, PMID 8493557 (abstract read via Europe PMC)
• Not yet verified: the source cell line and protein size (not in the abstract); the exact publication date (issue of 21 May 1993 not checked); the first animal-model protection papers (out of scope here).