Cell and gene therapies are emerging as potential treatments for Alzheimer's disease (AD), with several companies and institutions actively developing advanced therapeutics. As Alzheimer's Disease Awareness Month concludes, a look back at recent progress reveals promising developments in this field. More than 6.9 million Americans currently live with Alzheimer's disease, a number projected to reach 13.8 million by 2060, according to the Alzheimer's Foundation of America. Over 11 million Americans provide unpaid care, totaling over 18.4 billion hours.
Lexeo Therapeutics' LX1001 Gene Therapy
Lexeo Therapeutics' LX1001, an adeno-associated virus (AAV) vector-based gene therapy, has shown a dose- and time-dependent impact on apolipoprotein E2 (APOE2) expression in patients with APOE4 homozygote AD. Interim data from a phase 1/2 open-label clinical trial (NCT03634007) also indicated a decrease in several cerebrospinal fluid (CSF) AD tau biomarkers and changes on tau PET. The data were presented at the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) conference. The trial included 15 patients across 3 ascending single-dose cohorts: 1.4x1010 gc/ml (n = 5), 4.4x1010 gc/ml (n = 4), 1.4x1011 gc/ml (n = 3), and a single fixed-dose cohort at 1.4x1014 gc (n = 3). Participants received prednisone for 8 weeks post-treatment. Inclusion criteria included APOE4 homozygous status, age of at least 50 years, positive amyloid PET, CSF biomarkers consistent with AD, and mild cognitive impairment or mild to moderate dementia due to AD.
LX1001 was deemed safe and well-tolerated, with no cases of amyloid-related imaging abnormalities (ARIA) reported. APOE2 expression in CSF was observed in all patients, with a dose- and time-dependent increase in APOE2e4 expression. A decrease in CSF t-tau and phosphorylated-tau181 was observed in 9 of 13 participants, along with a decrease in CSF p-tau217 and p-tau231. No directional trend was observed in CSF amyloid-β42/40 or amyloid PET.
Lomecel-B Cell Therapy
Lomecel-B was well-tolerated in patients with mild AD receiving up to 4 infusions, demonstrating some improvements in cognitive function and other disease measures, according to data from the phase 2a CLEAR MIND trial (NCT05233774). These data were presented at the 2024 Alzheimer’s Association International Conference (AAIC). The trial included 49 participants: 12 in the placebo arm, 13 in the low dose arm (1 dose x 25 million), 13 in the low, multi-dose arm (4 doses x 25 million), and 11 in the high, multi-dose arm (4 doses x 100 million). No serious adverse events (AEs) related to Lomecel-B were reported. Serious AEs that did occur included acute respiratory failure, anemia, and lumbar radiculopathy, all of which resolved. There were no early discontinuations of infusion or any evidence of amyloid-related imaging abnormalities (ARIA).
NKGen Biotech's SNK01 NK Cell Therapy
NKGen Biotech is progressing its clinical trial of SNK01 natural killer cell (NK) therapy into a phase 2 trial in people with AD, following a positive safety review of phase 1 data. SNK01 is an autologous NK cell therapy with enhanced cytotoxicity and activating receptor expression. The therapy was previously assessed in the phase 1 ASK-AD trial (NCT04678453), which demonstrated that 4 doses of 1, 2, or 4 billion SNK01 cells administered intravenously was safe and crossed the blood brain barrier to reduce amyloid, tau, and alpha-synuclein proteins. Investigators also observed a dose-dependent decrease in neuroinflammation, and 90% of patients had improvements or maintenance in cognitive function as assessed by Alzheimer's disease composite score (ADCOMS).
Regeneration Biomedical's RB-ADSC Stem Cell Therapy
The first patient has been dosed in Regeneration Biomedical’s phase 1 clinical trial (NCT05667649) for RB-ADSC, an autologous, Wnt-activated adipose-derived stem cell therapy, for the treatment of AD. The first-in-human, open-label, single-arm trial is expected to enroll 9 participants over the course of a year, treated in a 3+3 dose escalation manner. The trial will evaluate safety and seek to establish a recommended dose for a possible phase 2 trial, with AD clinical assessments and evaluations of biochemical and anatomical biomarkers serving as secondary outcome measures. The study is recruiting patients aged 45 to 80 years of age with mild-to-moderate AD, with plans to follow patients for up to 12 months post-treatment. No side effects or adverse events have been reported to date.
