CTE Biologics, Inc.

Disclosed are therapeutic compounds, protocols, and compositions of matter useful for treatment of neurological conditions. In one embodiment the invention teaches the treatment of chronic traumatic encephalopathy (CTE) through protecting/regenerating the endothelial by administration of cells such as stem cells. In one embodiment stem cells are administered in order to protect the endothelium from apoptosis and to preserve the blood brain barrier. In another embodiment stem cells are administered together with endothelial progenitor cells in order to regenerate neural endothelium. In other embodiments preservation of brain integrity in conditions of degeneration is accomplished by administration of stem cells and/or endothelial cells.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority to U.S. Provisional Application No. 63/105,964, filed Oct. 27, 2020, the contents of which are hereby incorporated by reference.

FIELD OF THE INVENTION

The invention pertains to the use of stem cells for protecting and regenerating neurological function. The teachings herein are useful for treatment of conditions such as chronic traumatic encephalopathy and schizophrenia.

BACKGROUND

Modern day study of CTE was publicized by the pioneer work of pathologist Bennett Omalu, when in 2005 he reported a representative case of a retired National Football (NFL) player with progressive neurological dysfunction [6]. According to Omalu, the term CTE includes dementia pugilistica and supplants the use of the term dementia pugilistica. Due to initial controversy, and implications of CTE on various sports, it has been said that CTE is a very peculiar condition, in part because according to some authors “it is unique among brain diseases in having a history of decades of organized opposition to its codification as an authentic or valid entity [7].”

About one-third of CTE cases are progressive, but clinical progression is not always sequential or predictable. The clinical symptoms vary extensively, which is probably due to multiple damage sites among athletes with the condition [8]. The severity varies from mild complaints, to severe deficits accompanied by dementia, Parkinson-like symptoms, and behavioral changes. Clinical symptoms include neurological and cognitive complaints together with psychiatric and behavioral disturbances. Early neurological symptoms may include speech problems and impaired balance, while later symptoms include ataxia, spasticity, impaired coordination, and extrapyramidal symptoms, with slowness of movements and tremor [8, 9]. Cognitive problems, such as attention deficits and memory disturbances, often become major factors in later stages of the disease, although may occur at varying times throughout the course of CTE. Psychiatric and behavioral problems include lack of insight and judgment, depression, disinhibition, euphoria, hypomania, irritability, aggressiveness and suicidal tendencies.

CTE is also unique because it is typically defined after the patient dies, based on autopsy examination of the brain. According to more recent criteria, there are 4 stages of CTE, all with increasing neuropathology [4, 8, 10-15].

In Stage 1 CTE, at the macroscopic level, the brain appears normal, however, immunohistochemistry reveals the presence of phosphorylated tau in a limited number of places in the brain, usually in lateral and frontal cortices, as well as proximal to small blood vessels in the depth of sulci. Although unclear, it is believed at a clinical level, patients with Stage 1 CTE appear generally asymptomatic, or in some situations exhibit short term memory deficiency In some cases mild depression and/or concurrent aggressiveness is exhibited.

In State 2 CTE, there are some distinct anatomical deviations that may be seen such as enlargement of lateral ventricles, cavum septum pellucidum with or without fenestration, as well as pallor of the locus coeruleus and substantia nigra. Using immunohistochemistry, depositions of phosphorylated tau can be seen deep in the sulci, and there is an emergent spreading pattern. Behaviorally, Stage 2 CTE is characterized by mood and behavioral symptoms which could include behavioral outbursts and more severe depressive symptoms.

In Stage 3 CTE, macroscopic abnormalities are highly visible. Also, global brain weight loss, mild frontal lobe and temporal lobe atrophy, and dilation of the ventricles is observed. In these patients, one half display septal abnormalities, including cavum septum pellucidum. Furthermore, immunocytochemistry reveals that tau pathology spreads, involving the frontal, temporal, parietal and insular cortices. At a clinical level these patients present with more cognitive deficits, including memory loss, executive functioning deficits, visuospatial dysfunction, and apathy.

In Stage 4 CTE, there is a major reduction in brain weight, with brains weighing up to 30% less than control brains when “age-matched”. Severe atrophy of the frontal, medial temporal lobes, as well as anterior thalami is observed, along with atrophy of the white matter tracts. The majority of Stage 4 patients have septal abnormalities. The spread of the p-tau affects most regions, including the calcarine cortex. At a clinical level, patients present with advanced language deficits, psychotic symptoms which include paranoia, motor deficits, and parkinsonism.

SUMMARY

The teachings herein include methods of preserving integrity of the blood brain barrier comprising: a) obtaining a patient at risk of blood brain barrier leakage, and/or already having leakage of said blood brain barrier; b) administering to said patient one or more cellular populations; c) assessing said patient and when necessary adjusting dose of said cellular populations.