Professor Andrew G. Engel (1930-2024)

On October 20, 2024 Andrew G. Engel, a pioneer of neuromuscular research and an inspiration to many myologists, died.

Born in Budapest, Hungary, Dr. Engel moved to the United States of America with his parents in 1940. He lived and worked in the US throughout his life. After a half-century of cutting-edge research, Engel was privileged to work in a field where you can help many disabled patients. He attended Medical School at McGill University, Montreal, Quebec in Canada, in 1955.

He first wanted to follow his father (an internist and radiologist) into medicine. His career changed in the years 1958-59 when he had to sign up for National Service; he was assigned to the Division of Neurology at the US Public Health Service in Bethesda, Maryland, and during that period he decided to become a neurologist.

After training in neurology at the Mayo Clinic in 1961-1962, and then in neuropathology at Columbia University, Dr. Engel conducted research in the field of myopathies and identified several new congenital myopathies, his main field of interest along with the metabolic myopathies.

Engel’s research involved ultrastructural analysis of muscle biopsies under the electron microscope.

To work out what was going wrong in myopathies he had an active laboratory at the Medical Science Building at Mayo Clinic, Rochester, Minnesota where I joined him in the ‘70.
His familiarity with the morphological reaction of skeletal muscle helped him to identify several novel congenital myopathies, which he called multicore disease, fingerprint body myopathy, and sarcotubular myopathy. In those years, he recognized the adult-onset form of acid maltase deficiency (Late-Onset Pompe Disease) in several patients. A further key breakthrough occurred by investigating a patient with lipid storage myopathy and myalgia where a defect was found in fatty acid oxidation in muscle, that was inhibited by carnitine deficiency.

The 1970s and 1980s were very productive decades for Engel, who focused on the pathomechanisms of various inherited and acquired myopathies of unknown etiology. In 1975, he and Jerusalem dismissed the then-prevailing hypothesis that Duchenne muscular dystrophy was caused by the vascular supply of the muscle. Engel also discovered with Bahram Mokri, using the electron microscope, breaks in the surface membrane of otherwise normal fibers, predicting their destruction by the entry of calcium-rich extracellular fluid.

He deduced that this was the underlying defect, a hypothesis supported by the discovery of the Duchenne muscular dystrophy gene, dystrophin in 1987.

In 1989, Engel and Ogasahara studied two sisters with lipid accumulation, excess mitochondria in muscle tissue, and encephalopathy, which they identified as due to coenzyme Q10 deficiency, and showed the beneficial effects of replacement therapy.

In 1990, he conducted a systematic study on congenital myasthenic syndromes with Margherita Milone and Xin-Ming Shen, and on myofibrillar myopathies with his colleague Duygu Selcen.

His awards include the Gaetano Conte Prize for Clinical Research from the Mediterranean Society of Myology in 1999, the Lifetime Achievement Award from the World Federation of Neurology in 2002, election to the Institute of Medicine in 2003, and the title of Doctor of the Year from the Myasthenia Gravis Foundation of America in 2010. He also received the Jerry Lewis Muscular Dystrophy Award.

In 2006, a symposium honoring Andrew G. Engel and Peter J. Dyck was held at the Mayo Clinic in Rochester, bringing together many of their colleagues who presented their research. The group included Paula Clemens, Jan de Bleeker, Marianne de Visser, William Kennedy, Paola Sandroni, Angelo Schenone, Simone Spuler and myself, who presented what we learned at his School.

His treatise Myology complements the growth in this field with his outstanding contributions to the field of muscle. In 2014, he gave an extraordinary lecture on congenital myasthenic syndromes, rare but difficult disorders whose molecular pathogenesis he explained at the 14 ICNMD in Nice.

I visited AG Engel after he moved to a new lab and met his colleagues Margherita Milone and Duygu Selcen in September 2017. After that, he gradually retired and devoted more time to his favorite hobbies, which included landscape photography, classical music and golf.

Corrado Angelini

University of Padova