We have discovered that a small peptide degrades the β-amyloid protein that causes Alzheimer's disease, and have named such an enzyme peptide "Catalytide". The discovery of Catalytide is scientifically extremely interesting because it overturns the conventional concept of enzymes and raises expectations for the development of therapeutic drugs for Alzheimer's disease and the use of small molecule peptides in various industries. The Catalytide Research Lab was founded with the mission of exploring the unlimited potential of Catalytide.

The number of patients with Alzheimer's disease (AD) and Parkinson's disease (PD) continues to increase in the aging society and has become a major social problem. Therefore, the development of effective therapeutic drugs for these diseases is urgently needed, but despite numerous development studies, no effective therapeutic drugs have yet been developed. We have shown that small peptides not only promote degradation and inhibit aggregation of amyloid-β, but also inhibit and disassemble α-synuclein aggregation, which causes PD. We believe that small peptides have the potential to be fundamental AD/PD drugs that can not only suppress the progression of AD/PD, but also improve the disease after its onset.

Recently, a humanized IgG1 monoclonal antibody (Lecanemab) against aggregates of amyloid beta (Aβ) has been approved as a new drug by the Ministry of Health, Labor and Welfare for its efficacy in "suppressing the progression of mild cognitive impairment and mild dementia due to Alzheimer's disease." However, its side effects and price could be problematic. On the other hand, Catalytide is a peptide, which 1) has fewer side effects and is cheaper than antibody drugs, 2) is ultimately broken down into amino acids and reused, 3) is effective for nasal administration, has low toxicity, and can be administered continuously, and 4) is easy to derivatize and modify. For these promising features, Catalytide is expected to be a new peptide drug, alternative to antibody drugs.

Current Projects

1.Development of Alzheimer's disease therapeutics

Alzheimer's disease slowly impairs memory and thinking ability, and as it progresses, patients become not recognizing even their family members and spending most of the time in bed. Alzheimer's disease is the most common cause of dementia in the elderly and is an irreversible, progressive brain disease without any effective treatment unfortunately. The drugs currently used to treat Alzheimer's disease do not change the progression of Alzheimer's disease itself. Therefore, there is a demand to develop a therapeutic drug as soon as possible, but despite a lot of research and development, no effective therapeutic drug has been developed to date. Expectations are high for aducanumab, which was recently approved by the U.S. Food and Drug Administration, but the approval is conditional, and there is some concern about possible side effects due to the nature of antibody drugs.

The onset of Alzheimer's disease is associated with the accumulation of aggregated and insoluble amyloid β in the brain (Figure 1). We demonstrated for the first time in the world that a short chain peptide (Catalytide) hydrolyzes insoluble amyloid β. We have also discovered short-chain peptides that promote the dissociation of aggregated amyloid-β and make it soluble. Furthermore, experiments using Alzheimer's disease model mice (APP knock-in AD model mice) revealed that JAL-TA9 (YKGSGFRMI), which consists of 9 amino acid residues and is the most active among Catalytides, hydrolyzes and reduces amyloid β in the brain. In addition, experiments using Alzheimer's disease model mice with Aβ25-35 intracerebroventricularly administered have confirmed that JAL-TA9 has a preventive effect before its onset and a therapeutic effect (improvement of cognitive function) after onset. It has been also revealed that JAL-TA9 can be therapeutically effective not only by intravenous injection but also by nasal administration.

2.Development of Parkinson's disease therapeutics

Parkinson's disease is caused by a decrease in dopamine due to a decrease in dopamine neurons. The decrease in dopamine neurons is related to the aggregation and accumulation of a protein called α-synuclein in dopamine neurons. Preventing the increase of α-synuclein aggregates is an important step to develop therapeutic drugs.

We have discovered aggregation-inhibiting and disaggregating peptides (LYZA-3 and YS-RD11) that suppress the accumulation of α-synuclein aggregates. Furthermore, experiments using Parkinson's disease model mice with Syn61-84 (a peptide consisting of amino acids 61 to 84 of α-synuclein) intracerebroventricularly administered showed that these peptides reduced deterioration of their motor function caused by administered Syn61-84. Because LYZA-3 and YS-RD11 are effective when administered both after and before the decline in motor function, they are expected to be used as therapeutic agents that can range from prevention to treatment.

3.Development of amyotrophic lateral sclerosis (ALS) therapeutics

Amyotrophic lateral sclerosis (ALS) is a disease that causes loss of ability to move muscles throughout the body due to damage to motor neurons, even though consciousness remains normal, leading to death within a short period of time after onset. No cure has been developed. The cause of ALS is thought to be that the steric structure of SOD1, a type of active oxygen, changes from a normal form to a highly toxic abnormal form and accumulates in spinal motor neurons. The details, however, have not been clarified yet.

We have confirmed that administering SOD1 fragment peptides into the tail vein of ICR mice causes ALS-like decline in motor function weight loss. Furthermore, we have discovered Catalytide, which hydrolyzes SOD1 fragment peptides, and are currently actively investigating the use of Catalytide as a treatment for ALS.

4.Development of IgA nephropathy therapeutics

IgA nephropathy is the most common cause of chronic glomerulonephritis, and 15-20% of adult-onset cases of IgA nephropathy lead to end-stage renal failure in 10 years and approximately 40% in 20 years. The cause of IgA nephropathy is said to be immune complexes like IgA modified with abnormal sugar chains, being deposited in glomerulus. Currently treatment is limited to corticosteroids and immunosuppressants to slow down the progress of the disease and is no cure.

We have confirmed that administering JAL-TA9 into the tail vein of mice reduces urinary protein and β2-microglobulin, which is an indicator of renal tubular damage. Furthermore, after euthanasia, their kidneys were removed and weighed, suggesting that kidney fibrosis was suppressed in the JAL-TA9-treated group. JAL-TA9 has a potential to be a therapeutic drug for IgA nephropathy by decomposing immune complexes deposited in kidneys. We are conducting basic experiments towards its development.


  1. T. Akizawa, T. Yamamoto, Novel peptide exhibiting hydrolytic activity and use thereof, PCT/JP2017/000341
    1-1. Same as above, JP Patent No. 7046349
    1-2. Same as above, US Patent No. 10,995,119
    1-3. Same as above, EP Patent Application No. 17736048 (Registered in UK, France, Germany, Switzerland)
    1-4. Same as above, CN Patent No. 108699122
  2. T. Akizawa, R. Nakamura, Amyloid-beta aggregation inhibitor, pharmaceutical composition for amyloid-beta aggregation disease, and use application of same, JP Patent Application No. 2020-167404
  3. T. Akizawa, M. Saito, R. Nakamura, Alpha-synuclein aggregation inhibitor, pharmaceutical composition for alpha-synuclein aggregation disease, and use application of same, JP Patent Application No. 2021-080512
  4. T. Akizawa, R. Nakamura, Amyloid-beta aggregation inhibitor, pharmaceutical composition for amyloid-beta aggregation disease, and use application of same, JP Patent Application No. 2021-080513