First-in-class treatment for early Parkinson’s shows ‘remarkable’ results

A new first-in-class treatment for Parkinson’s disease, designed to get past the brain’s protective barrier, was shown to be safe and well-tolerated in an early clinical trial, and to have “robust [central nervous system] exposure.”

That’s according to new data from the Phase 1 trial, which involved both patients and healthy volunteers, testing Teitur Trophics‘ TT-P34 for early-stage Parkinson’s. In a company press release announcing the study’s “successful results,” the developer said its experimental therapy “has potential as a disease-modifying drug.”

Pharmacological and biomarker data from the study suggest that TT-P34 is entering the brain and modulating cell activity as expected, according to Teitur. The company is already planning further testing of the injection therapy.

“These are remarkable results from our Phase 1 clinical trial of TT-P34 in healthy volunteers and patients with early-stage Parkinson’s disease,” said Simon Mølgaard, PhD, Teitur’s cofounder and CEO.

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Parkinson’s is marked by the death and degeneration of brain cells that produce dopamine, an important chemical messenger. Low dopamine levels lead to both the motor symptoms and nonmotor symptoms that characterize the disease. Standard treatment involves levodopa-based therapies, which aim to boost dopamine levels and may ease symptoms but do not affect disease progression.

The causes of Parkinson’s are not fully understood, but at the cellular level, the disease is typically marked by toxic clumps of proteins that are thought to drive disease worsening. Normally, cells dispose of unneeded proteins via the lysosome, a cellular compartment that acts like a molecular garbage disposal, chopping them into simple components that can be recycled or repurposed.

Parkinson’s therapy TTP-34 tested in patients, volunteers

TTP-34 is a peptide or small protein that’s designed to activate CREB, which is a transcription factor — a type of molecular machinery that helps control gene activity. By increasing CREB activity, the therapy aims to activate genes that support lysosomal function, thereby enhancing cells’ ability to dispose of unneeded proteins. CREB activation is also expected to boost mitochondrial activity, the cellular organelles that provide cells with energy.

To evaluate the safety and pharmacological properties of TTP-34, Teitur conducted a Phase 1 trial at the Centre for Human Drug Research in the Netherlands. In the first part of the study, 31 healthy volunteers received single subcutaneous, or under-the-skin, injections of the therapy or a placebo at various doses. Then, another 24 healthy volunteers received multiple injections at various doses. The study also tested TTP-34 in a dozen people with early-stage Parkinson’s.

Safety data showed the therapy was, overall, tolerated well, Teitur said. There were no dose-limiting toxicities, which are side effects that suggest a medication dose is too high to be safe. Further, TTP-34 was well tolerated when coadministered with standard-of-care levodopa in participants with Parkinson’s.

Pharmacological data showed that TTP-34 can cross the blood-brain barrier, a cellular wall that normally helps prevent toxins in the blood from entering the brain. According to Teitur, the results support weekly dosing of TTP-34 for future testing.

These data show TT-P34 — which is potentially a game-changer not just for Parkinson’s disease but a range of other neurodegenerative diseases as well — has an excellent safety profile and … enters the brain … as expected.

Analyses of cerebrospinal fluid, which surrounds the brain and spinal cord, indicated changes in the levels of several proteins, according to the developer. That suggests that TTP-34 treatment increased lysosomal function as intended, per Teitur.

“These data show TT-P34 — which is potentially a game-changer not just for Parkinson’s disease but a range of other neurodegenerative diseases as well — has an excellent safety profile and … enters the brain … as expected,” said Andreas Borta, PhD, Teitur’s chief medical officer. Borta said “the biomarker data, which indicate engagement of the lysosomal pathway, are also highly encouraging,” adding that the drug has “excellent” pharmacological properties.

Teitur is planning to present detailed results from the trial at a medical conference next month. The company said it is hoping to launch a Phase 2 clinical trial next year to further test TTP-34’s potential in people with Parkinson’s.

“We are now fundraising for a Series B investment round ahead of our planned [Phase 2] study of TT-P34 in Parkinson’s,” Mølgaard said. “Disease-modifying treatments for Parkinson’s, a condition that seriously affects over 10 million people worldwide, are desperately needed as we can still only manage its symptoms.”