Tetra Discovery Partners is a clinical stage biotechnology company developing innovative products that address unmet medical needs such as in Fragile X Syndrome and Alzheimer’s disease. Tetra’s mission is to restore clarity of thought in people affected by Fragile X Syndrome, Alzheimer’s disease, or other conditions that impair human brain function.

How the Brain Forms Memories

The brain forms memories by creating new connections between neurons. When memories are created, the first stage is transient and short term. Short term memory can be disrupted by trauma (concussion), epileptic seizure, alcohol or drugs. Short term memories are converted into long term memories through the formation and stabilization of new connections between neurons.

Memories are lost when the connections between neurons are lost. This is a normal process, not every memory is important and marked for saving. As we age, new memories may also overwrite older memories.

Addressing Memory Formation and Impaired Cognition

Alzheimer’s disease and Fragile X Syndrome both affect how the brain forms and stabilizes connections between neurons. In the case of Fragile X Syndrome, connections between neurons do not mature the way they should. In Alzheimer’s disease, connections are lost prematurely due to the disease process.

Through scientific innovation, Tetra has developed a compound, or investigational new drug, named BPN14770. BPN14770 is designed to treat behavior and cognition in Fragile X Syndrome patients and memory loss in early-to-moderate Alzheimer’s disease patients. BPN14770 is thought to help promote the maturation and stabilization of brain connections. Tetra is putting BPN14770 through clinical trials to discover if it has a positive impact on both Alzheimer’s disease, when connections are lost, and in Fragile X Syndrome, where connections between neurons are not mature.

Tetra Discovery Partners, Inc. is committed to building a leading portfolio of clinical trial stage treatments, based on phosphodiesterase sub-type inhibitors for both neuroscience and non-neuroscience disorders. These are fields in which we believe Tetra is poised to deliver multiple novel treatments, with the potential to change patients’ lives.

What is the science behind BPN14770?

BPN14770 is the result of Tetra’s pursuit to selectively inhibit one of the phosphodiesterase (PDE) enzymes. Tetra is a leader in the chemical design of inhibitors of PDE4 enzymes in the brain. There are four PDE4 enzymes in the body: PDE4A, PDE4B, PDE4C, and PDE4D.

Tetra Discovery’s current work is focused on PDE4D (for Fragile X Syndrome and Alzheimer’s Disease) and PDE4B (for cognitive impairment stemming from traumatic brain injury).

The focus on PDE4D

Tetra’s investigational new drug, named BPN14770, can selectively target and inhibit, or suppress, only the PDE4D enzyme.

PDE4D plays an important role in cognition. A recent study of over a million healthy human subjects showed connections between genetic variants in PDE4D and years of educational attainment and performance on cognitive tests.

Very rare mutations in PDE4D cause intellectual disability in children. We also know that genetic variation in PDE4D contributes to variation in healthy brain function.

Prior to now, attempts to target the PDE4 enzymes have addressed all four of the enzymes at once, producing unwanted side effects in the patient, such as nausea, vomiting, and diarrhea. Because Tetra has discovered how to selectively target just one of these enzymes, specifically PDE4D, clinical trials will show if BPN14770 will be a well-tolerated and effective new medicine.

Tetra seeks to inhibit enzymes in the brain when cognition is impaired. Cognitive impairment occurs when synapses within the brain do not communicate properly at a cellular level. Cognitive problems occur when there is too much activity, or not enough—when neurons do not signal properly. Within brain cells, the substance which controls the way synapses communicate is cyclic AMP, or cAMP.

Tetra’s science builds on previous work by Nobel laureates that identified PDE4 as a key enzyme that shapes proper cAMP signaling. Specifically, PDE4 limits the spread of cAMP so that spatial and temporal patterning of information is maintained.

Tetra Discovery’s BPN14770 targets only PDE4D, and only at specific times of cellular activity. BPN14770 is designed to modulate, rather than completely inhibit, PDE4D. The desired result from clinical trial testing is two-fold: that Tetra’s BPN14770 will improve cognitive function by prolonging cAMP activity, while safety and tolerability are improved because the enzyme is not completely inhibited.

The focus on PDE4B

Traumatic brain injury can also cause memory loss. The cAMP/protein kinase A/pCREB signaling pathway is down-regulated after traumatic brain injury.

The PDE4B enzyme plays an important role during inflammation. Inhibition of PDE4B reduces inflammation in the body. Drugs that inhibit PDE4B (as well as the other PDE4 enzymes) have been shown to be effective treatments for psoriasis, psoriatic arthritis and atopic dermatitis. The PDE4B enzyme also plays an important role during inflammation in the brain, for example, after traumatic brain injury. In animal models of brain injury, PDE4B inhibitors reduce inflammation and can help restore healthy brain function.

Tetra Discovery’s focus is to address the functioning of PDE4s to enhance memory formation in brain neurons, brain microglia involved in brain inflammation, and nerve dendrites involved in schizophrenia and depression. Tetra’s drug discovery platform can also be used to develop novel treatments for peripheral diseases where PDEs are attractive drug targets. These include Huntington’s disease, Parkinson’s disease, schizophrenia, and major depression.