NJ Biotech’s Compound May Bypass Stop Mutations, Trigger Protein Expression
A small biotech company in New Jersey may soon begin human trials for a drug candidate that works by counteracting premature stop mutations believed to be linked to cystic fibrosis and muscular dystrophy.
The experimental compound, PTC124, was designed to manufacture a version of a protein that would otherwise not be expressed due to the mutation.
Researchers at the company, PTC Therapeutics, said the therapy would not affect other genes because their stop codon exists at the tail of the mRNA, rather than the middle — which is where stop mutations exist.
Though results from the company’s findings have yet to be published — it has yet to initiate trials in humans — preclinical results lead PTC to believe that the compound may be safer and more readily absorbed than the commonly used antibiotic gentamicin, which has been found to have a serendipitous ability to make proteins blocked by stop mutations.
Indeed, research published in the Oct. 9 New England Journal of Medicine found that gentamicin, also known as Garamycin and made by Schering-Plough, usurps stop mutations and allows cells to manufacture a protein, in this case CTFR, which protects against the development of cystic fibrosis. Other research has showed that the antibiotic can induce the production of dystrophin protein in patients with muscular dystrophy.
However, gentamicin is poorly absorbed, according to a report in New Scientist. The news outlet said that pre-clinical tests of PTC124 “indicate that it is more potent than gentamicin and seems to have very low toxicity. “This could have very far-reaching effects,” David Bedwell, a microbiologist at the University of Alabama in Birmingham, who has tested the compound in his lab and is collaborating with the company, was quoted in New Scientist as saying.
In its study, PTC Therapeutics studied the compound in mice with muscular dystrophy and found it to restore dystrophin expression on the surface of muscle cells, according to New Scientist. “Tests suggest the muscles regain some of their normal characteristics” while tests on mice with cystic fibrosis “also suggest PTC124 restores production of functional CFTR,” the report said.
The report went on to say that PTC Therapeutics “hope[s] to publish as soon as intellectual property issues are resolved.” The news service said that chief medical officer Langdon Miller hopes to launch clinical trials with healthy volunteers next year.
UNESCO Adopts International Declaration on Genetic Data
The United Nations Educational, Scientific, and Cultural Organization has adopted the International Declaration on Human Genetic Data.
The declaration, made at UNESCO’s General Conference meeting in Paris last week, outlines ethical principles that should govern the collection, processing, storage, and use of human genetic data. It was written in response to the growing number of national genetic banking projects, UNESCO said.
Because governments are turning to genetic data to resolve questions of paternity or criminal cases, common ethical guidelines needed to be defined, the group said. “I could never overstate the urgency with which we must adopt such a declaration, because every day brings more new experiments and initiatives, some of which could have irreversible consequences,” said Koïchiro Matsuura, UNESCO director-general, in his speech to the General Conference on Sept. 30.
“Every effort should be made to ensure that human genetic data and human proteomic data are not used for purposes that discriminate in a way that is intended to infringe, or has the effect of infringing human rights, fundamental freedoms or human dignity of an individual or for purposes that lead to the stigmatization of an individual, a family, or a group or communities,” one of the provisions of the declaration reads.
The declaration, which can be read here, is not a legally binding instrument, but was chosen instead of a convention “to facilitate consensus and allow for adaptations in a domain where the variety of situations covered, and the complexity of the subject, is constantly evolving with new scientific discoveries,” the UNESCO statement explained.
It elaborated: A “person’s identity should not be reduced to genetic characteristics, since it involves complex educational, environmental and personal factors and emotional, social, spiritual and cultural bonds with others and implies a dimension of freedom.”
The declaration calls for collecting, treating, using, and storing genetic data using transparent and ethically acceptable procedures. It proposes that independent, multidisciplinary ethics committees be established at national, regional, local, or institutional levels.
At the collection stage, the declaration emphasizes “prior, free, informed and express consent, without inducement by financial or other personal gain” of the person providing the data.